A disturbance of prostaglandin metabolism is currently believed to be one of the major mechanisms in the pathogenesis of preeclampsia. Most previous studies of this theory, however, have included only women who had already developed clinically overt disease. In order to investigate whether prostaglandin abnormalities precede the onset of preeclampsia, we have designed a nested case-control study using stored urine specimens prospectively collected as early as thirteen weeks gestation from women participating in the NICHD Trial of Calcium to Prevent Preeclampsia (CPEP). In this study, we compared the urinary excretion of prostacyclin and thromboxane in preeclampsic women before the diagnosis of preeclampsia to that in normal pregnant women at comparable gestational ages. Data analysis demonstrated that in women who go on to develop preeclampsia, reduced prostacyclin production occurs months before any clinical sign of preeclampsia. The ratio of vasoconstricting to vasodilating eicosanoids is significantly higher in women who will later develop preeclampsia.